Acne and group A strep: an unknown burden

痤疮和 A 组链球菌：未知的负担

• 批准号: 6864401
• 负责人: David Margolis
• 金额: $ 58万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-19 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6864401
• 关键词: Streptococcus infection; Streptococcus pyogenes; acne; antiinfective agents; clinical research; drug administration rate /duration; epidemiology; human subject; microorganism interaction; respiratory infections; therapy adverse effect; university student

DESCRIPTION (provided by applicant): Acne vulgaris is an illness that afflicts adolescents and young adults. About 20% of those with acne, who seek medical care, are severe enough to require systemic therapy. Those on antibiotics receive about 9.7 million prescriptions for oral antibiotics and about 8.2 million for the topical antibiotics. Therapy frequently continues for more than 6 months. Simply stated, very large quantities of antibiotics are used for an extended period of time by this sector of the population. The burden of both acne and acne therapies, as with all skin diseases, on society and the patient has not been well described as discussed at a recent NIAMS conference. We have recently demonstrated that antibiotic therapy for ache when given topical and/or orally to young adults may profoundly affect an individual's likelihood of being colonized with group A streptococcus (GAS), the main bacterial cause of pharyngitis. Upper respiratory tract infections, including pharyngitis, are extraordinarily common acute medical problems that are primarily of viral origin, are self-limited acute condition, and are generally mild but have huge public health implications due to the shear magnitude of numbers of individuals afflicted. In fact, the US economic cost is estimated to be more than 25 billion dollars per year. There are very few natural models of truly long-term human antibiotic use. Acne is a model of a disease for which long-term antibiotic use is standard and appropriate therapy. In this proposal, we will explore possible mechanisms that may be responsible for the increase in oro-pharyngeal colonization of GAS that we have noted in individuals who use antibiotics (oral and/or topical) for acne. We believe that the antimicrobial effect is through the elimination of competing normal bacterial flora. In fact, GAS in the oro-pharynx has been shown to be "regulated" by another organism, like S. Salivarius. Epidemiologically, very little is known about the association of changes in the normal flora of the throat and how this may impact the acquisition and chronic carriage of GAS, or whether these changes are associated with an infectious illness (i.e., pharyngitis). Persistent colonization, potentially does not only put the patient at risk but increases the risk of spread of GAS to close contacts. Persistent colonization of GAS also increases the likelihood of GAS acquiring resistance directly and horizontally from related species. Finally, with respect to bioterrorism post-exposure prophylaxis with antibiotics such as the tetracyclines, which are used to treat acne, will need to be maintained for prolonged periods of time (6 to 8 months). There is currently very limited data on the long-term consequences of tetracycline use. With respect to all of these issues, acne patients represent a great model to study regarding both the long-term toxicity of antibiotics and the risks of increasing resistance among bacterial pathogens exposed to drugs during treatment. We hypothesize that the use of long-term antibiotics for acne can result in oropharyngeal colonization with GAS and that this colonization can result in morbidity. To that end, we describe studies to help us understand who is at risk for colonization with GAS, the likelihood that these individuals will be persistently colonized, and the likelihood that individuals on antibiotics will develop pharyngitis.

描述（由申请人提供）：寻常痤疮是一种困扰青少年和年轻人的疾病。大约20%的痤疮患者寻求医疗护理，严重到需要系统治疗。使用抗生素的人收到约970万份口服抗生素处方和约820万份外用抗生素处方。治疗通常持续6个月以上。简单地说，这部分人口长期使用大量抗生素。痤疮和痤疮治疗的负担，与所有皮肤病一样，对社会和患者的影响并没有得到很好的描述，正如最近的NIAMS会议上所讨论的那样。我们最近已经证明，抗生素治疗疼痛时，给予局部和/或口服的年轻人可能会深刻地影响一个人的可能性被定植与A组链球菌（GAS），咽炎的主要细菌原因。上呼吸道感染，包括咽炎，是非常常见的急性医学问题，其主要是病毒来源，是自限性急性病症，并且通常是温和的，但由于患病个体数量的剪切量级而具有巨大的公共卫生影响。事实上，美国每年的经济损失估计超过250亿美元。很少有真正长期使用人类抗生素的自然模型。痤疮是一种疾病的模型，长期使用抗生素是标准和适当的治疗方法。在本提案中，我们将探讨可能导致GAS口咽定植增加的可能机制，我们在使用抗生素（口服和/或外用）治疗痤疮的个体中注意到了这一点。我们认为，抗菌作用是通过消除竞争正常细菌植物群。事实上，口咽部的GAS已经被证明是由另一种生物体“调节”的，如S。唾液流在流行病学上，关于咽喉的正常植物群的变化的关联以及这可能如何影响GAS的获得和慢性携带，或者这些变化是否与感染性疾病（即，咽炎）。持续的定植不仅可能使患者处于危险之中，而且会增加GAS传播给密切接触者的风险。GAS的持续定殖也增加了GAS直接和水平地从相关物种获得抗性的可能性。最后，关于生物恐怖主义，使用抗生素（如治疗痤疮的四环素）进行接触后预防，需要维持较长时间（6至8个月）。目前关于四环素使用的长期后果的数据非常有限。关于所有这些问题，痤疮患者代表了一个很好的模型，可以研究抗生素的长期毒性和治疗期间暴露于药物的细菌病原体的耐药性增加的风险。我们假设长期使用抗生素治疗痤疮可导致GAS在口咽部定植，这种定植可导致发病。为此，我们描述了一些研究，以帮助我们了解哪些人有GAS定植的风险，这些人持续定植的可能性，以及抗生素使用者发生咽炎的可能性。